It is the purpose of this project to better understand the mechanism of the ionic conductances in membranes which are voltage dependent, i.e., excitable. One of the methods is to study the effect of chemicals which interact with ionic channels, in order to find out more about the channels. In particular, we want to learn where the voltage-dependent gates are located and how the gates respond to electric field. Currently, we are studying yohimbine which changes the voltage-dependent sodium conductance in the membrane of the squid giant axon. We are especially interested in the site of yohimbine binding to the membrane. Other studies designed to learn more about the mechanism of voltage-dependent conductance are: 1) The effect of pressure of axonal and synaptic membranes of the squid. 2) The effects of membrane potential on the calcium channel in the barnacle muscle membrane.